丹酚酸B调控Nrf2/ARE通路在博莱霉素诱导肺纤维化中的保护机制研究

项目名称： 丹酚酸B调控Nrf2/ARE通路在博莱霉素诱导肺纤维化中的保护机制研究

项目编号： No.81470179

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李青

作者单位： 南京中医药大学

项目金额： 73万元

中文摘要： 肺纤维化是由多种病因引起的肺破坏性疾病，目前西医尚无有效药物。中医认为气血不通，络脉瘀阻是肺痹和肺痿的发病原因。中药丹参具有活血化瘀，通心包络之功效，常用来对肺痹和肺痿进行调理，并具有良好的治疗效果。Nrf2/ARE通路在肺纤维化中的作用已被证实。课题组建立了基于荧光素酶报告基因检测技术的Nrf2中药活性成分筛选平台，从丹参多种成分中筛选得到丹参酸B。利用博莱霉素诱导的肺纤维化模型，采用分子生物学手段对比丹参酸B在Nrf2基因敲除小鼠（Nrf2-/-）和野生型小鼠（Nrf2+/+）肺纤维化中对肺组织的保护作用，揭示丹参酸B通过调控Nrf2/ARE通路对肺纤维化组织进行保护及丹参酸B激活Nrf2的相关信号机制。本研究有利于丹参提取物的开发和临床应用，为中医药防治肺纤维化提供新思路和新方法。

中文关键词： 丹参酸B；肺纤维化；上皮间质转化；氧自由基；核因子E2相关因子2

英文摘要： Pulmonary fibrosis is a group of lung devastating disease caused by various complicated factors. Traditional Chinese medicine believes that Qi and blood obstruction and collateral vessel blood-stagnation is the reason for pulmonary fibrosis. They always use the salvia to treat these patient since the salvia plays an important role in promoting blood circulation and removing blood stasis. The salvia is a natural antioxidant substances has been confirmed in recent years, however, the therapeutic mechanism of pulmonary fibrosis was unclear. The important role of Nrf2/ARE signaling pathway in pulmonary fibrosis development has been confirmed by numerous research experiments. Our group had established an Nrf2 dual luciferase reporter screening platform, the salvia ingredients were screened by this platform and luckly found salvianolic acid B (Sal B). Firstly, we plan to use Nrf2 +/+ and Nrf2 -/- mouse to induce pulmonary fibrosis model. Secondly, make observation of a) pulmonary fibrosis lung tissue protective effect of Sal B in bleomycin-induced Nrf2+/+ and Nrf2-/- mouse model, b) TGF-β-induced migration and differentiation of epithelial cells in mice after Sal B intervention, c) make detection of the changes of Nrf2 expression after the Sal B interferences and the changes of MAPK, PKC, ERK, PI3K, P21, P62, NQO1, γ-GCS and HO-1 expression via immunofluorescence double staining, Western blot, qPCR methods. We supposed to make a prove of the protective effect and mechanism of Nrf2/ARE in the lung tissue by Sal B and activation of Nrf2 signal transduction mechanisms by Sal B. This study is conducive to the development and clinical application of Sal B, and conduct new ideas and new ways for chinese medicine in prevention and treatment of pulmonary fibrosis.

英文关键词： Salvianolic acid B;Pulmonary fibrosis;Epithelial-mesenchymal transition;ROS;Nrf2